title: Integrative analysis of congenital muscular torticollis: from gene expression to clinical significance.
abstract: BACKGROUND
  Congenital muscular torticollis (CMT) is characterized by thickening and/or tightness of the unilateral sternocleidomastoid muscle (SCM), ending up with torticollis. Our aim was to identify differentially expressed genes (DEGs) and novel protein interaction network modules of CMT, and to discover the relationship between gene expressions and clinical severity of CMT.
  
  
  RESULTS
  Twenty-eight sternocleidomastoid muscles (SCMs) from 23 subjects with CMT and 5 SCMs without CMT were allocated for microarray, MRI, or immunohistochemical studies. We first identified 269 genes as the DEGs in CMT. Gene ontology enrichment analysis revealed that the main function of the DEGs is for extracellular region part during developmental processes. Five CMT-related protein network modules were identified, which showed that the important pathway is fibrosis related with collagen and elastin fibrillogenesis with an evidence of DNA repair mechanism. Interestingly, the expression levels of the 8 DEGs called CMT signature genes whose mRNA expression was double-confirmed by quantitative real time PCR showed good correlation with the severity of CMT which was measured with the pre-operational MRI images (R2 ranging from 0.82 to 0.21). Moreover, the protein expressions of ELN, ASPN and CHD3 which were identified from the CMT-related protein network modules demonstrated the differential expression between the CMT and normal SCM.
  
  
  CONCLUSIONS
  We here provided an integrative analysis of CMT from gene expression to clinical significance, which showed good correlation with clinical severity of CMT. Furthermore, the CMT-related protein network modules were identified, which provided more in-depth understanding of pathophysiology of CMT.
authors.affiliation: The Center for Torticollis, Department of Physical Medicine and Rehabilitation, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Shin-Young
authors.initials: SY
authors.lastname: Yim
authors.forename: Dukyong
authors.initials: D
authors.lastname: Yoon
authors.forename: Myong Chul
authors.initials: MC
authors.lastname: Park
authors.forename: Il Jae
authors.initials: IJ
authors.lastname: Lee
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Lee
authors.forename: Kyu-Sung
authors.initials: KS
authors.lastname: Kwack
authors.forename: Jan-Dee
authors.initials: JD
authors.lastname: Lee
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Lee
authors.forename: Euy-Young
authors.initials: EY
authors.lastname: Soh
authors.forename: Young-In
authors.initials: YI
authors.lastname: Na
authors.forename: Rae Woong
authors.initials: RW
authors.lastname: Park
authors.forename: KiYoung
authors.initials: K
authors.lastname: Lee
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Jun
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014103:Torticollis / Q000151:congenital* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger